Three classes of peptide neurotoxins from the venom of marine snails of the genus Conus and the ion channel targets of these toxins will be examined in this study. They are as follows: alpha conotoxins-nicotinic acetylcholine receptors; omega conotoxins-voltage-gated (synaptic) calcium channels; and conantokins-glutamate (NMDA) receptors. Fluorescent derivatives of the toxins will be synthesized, functionally characterized by electrophysiological assays, and used as probes in a novel approach for analyzing ligand-receptor binding. The new approach to assess binding works with nanomolar concentrations of ligand and receptor in nanoliter volumes; hence, it is referred to as a "nanoassay." The approach is simple both in concept and execution. It requires a fluorescent ligand and employs a microscope as a microfluorometer to measure the ligand's concentration within a microscopic speck of a steric exclusion matrix, such as a polyacrylamide or dextran bead. The matrix is permeable to the small ligand but not to its larger receptor, therefore, receptor-bound, but not free, ligand is excluded from the matrix. Thus, the approach is called fluorescent ligand exclusion analysis (FLEA). The FLEA approach circumvents the need to mechanically separate bound from unbound ligand (a major shortcoming of more conventional methods). It is fast-measurements can be performed in seconds and, in principle, "on line". FLEA will be further developed and used to examine conotoxin-receptor binding. These experiments characterizing toxin binding will complement the electrophysiological experiments assessing toxin function. Although FLEA was originally conceived as a means to assess the binding of neurotoxins with their targets, the approach can also be used to examine ligand-receptor interactions in a variety of other systems. For examples: of antigen with antibody; of nucleic acid with nucleic acid or protein; of drug, hormone, or transmitter with receptor; and of substrate with enzyme. A major impetus for the further development of the FLEA approach is its potential broad utility. Furthermore, in view of its relative simplicity and sensitivity, FLEA may even have application in clinical laboratories.